The Genetics Clinic is a collaborative undertaking by researchers from five different institutes and the Clinical Center. Consequently, Clinic patients constitute a broad spectrum of genetic disease. The patient load during the Clinic's second year comprised 300 individuals representing 60 different diagnostic categories. Of these, 97 patients (32%) were seen by members of CEB. For our Branch the Clinic provides a multidisciplinary setting in which to study unusual patients who either have cancer or increased risk of developing malignancy. Patients are ascertained through special referrals from outside physicians and inhouse requests for etiologic consultations. With informed consent, the approach to the patient includes detailed physical examination and, where applicable, epidemiologic studies of the environmental and genetic background and laboratory studies to clarify biologic mechanisms of carcinogenesis. Categories include patients with neurofibromatosis, a common autosomal dominant disorder that has an increased predisposition to cancer, patients with birth defects and cancer families with childhood sarcomas and breast cancer in blood relatives, and any other families with an excessive occurrence of cancer of any type.